Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.

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Application of chemical fertilizer or manure can affect soil microorganisms directly by supplying nutrients and indirectly by altering soil pH. However, it remains uncertain which effect mostly shapes microbial community structure. We determined soil bacterial diversity and community structure by 454 pyrosequencing the V1-V3 regions of 16S rRNA genes after 7-years (2007–2014) of applying chemical nitrogen, phosphorus and potassium (NPK) fertilizers, composted manure or their combination to acidic (pH 5.8), near-neutral (pH 6.8) or alkaline (pH 8.4) Eutric Regosol soil in a maize-vegetable rotation in southwest China. In alkaline soil, nutrient sources did not affect bacterial Operational Taxonomic Unit (OTU) richness or Shannon diversity index, despite higher available N, P, K, and soil organic carbon in fertilized than in unfertilized soil. In contrast, bacterial OTU richness and Shannon diversity index were significantly lower in acidic and near-neutral soils under NPK than under manure or their combination, which corresponded with changes in soil pH. Permutational multivariate analysis of variance showed that bacterial community structure was significantly affected across these three soils, but the PCoA ordination patterns indicated the effect was less distinct among nutrient sources in alkaline than in acidic and near-neural soils. Distance-based redundancy analysis showed that bacterial community structures were significantly altered by soil pH in acidic and near-neutral soils, but not by any soil chemical properties in alkaline soil. The relative abundance (%) of most bacterial phyla was higher in near-neutral than in acidic or alkaline soils. The most dominant phyla were Proteobacteria (24.6%), Actinobacteria (19.7%), Chloroflexi (15.3%) and Acidobacteria (12.6%); the medium dominant phyla were Bacterioidetes (5.3%), Planctomycetes (4.8%), Gemmatimonadetes (4.5%), Firmicutes (3.4%), Cyanobacteria (2.1%), Nitrospirae (1.8%), and candidate division TM7 (1.0%); the least abundant phyla were Verrucomicrobia (0.7%), Armatimonadetes (0.6%), candidate division WS3 (0.4%) and Fibrobacteres (0.3%). In addition, Cyanobacteria and candidate division TM7 were more abundant in acidic soil, whereas Gemmatimonadetes, Nitrospirae and candidate division WS3 were more abundant in alkaline soil. We conclude that after 7-years of fertilization, soil bacterial diversity and community structure were shaped more by changes in soil pH rather than the direct effect of nutrient addition.

Polydopamine (PDA) coating as a bioinspired strategy for nanoparticles (NPs) has been extensively applied in cancer theranostics. However, a cellular-level understanding of nano-biointeraction of these PDA-coated NPs (PDNPs), which drives the fate of them and acts as a critical step to determine their efficacy, still remains unknown. Herein, we utilized the representative mesoporous silica NPs (MSNs) to be coated with PDA and study their nano-bioactivities in cancer cells. HeLa cell line was utilized as a model in this study. The PDNPs were discovered to be internalized through three specific pathways, that is, Caveolae-, Arf6-dependent endocytosis, and Rab34-mediated macropinocytosis (55%, 20% and 37% of uptake inhibition by nystatin, Arf6 knockdown, and rottlerin, respectively). Autophagy-mediated accumulation of PDNPs in lysosomes was observed and the formed PDA shells shedded in the lysosomes. Almost 40% of the NPs were transported out of cells via Rab8/10- and Rab3/26-mediated exocytosis pathways at our tested level. On the basis of these results, a novel combined cancer treatment strategy was further proposed using drug-loaded MSNs-PDA by (i) utilizing naturally intracellular mechanism-controlled PDA shedding for organelle-targeted release of drugs in lysosomes to generate lysosome impairment and (ii) blocking the demonstrated exocytosis pathways for enhanced therapeutic efficacy.